In this proposed study labeled cocaine will be synthesized to study its mode of metabolism. Special attention will be placed on the distribution of cocaine and metabolites and on any changes in the metabolic fate of cocaine following chronic administration for possible correlation with the neurochemical changes and the increased excitatory behavior induced by prolonged treatment with the drug. Distribution and metabolism of cocaine will also be studied in maternal and fetal tissues to ascertain possible untoward effects to the fetus when the drug is given during pregnacy. The involvement of biogenic amines and cyclic AMP in the behavior of both acutely or chronically cocaine-treated animals will be explored. The interactions of cocaine with barbiturates and chlorpromazine will be studied for further understanding of the action of cocaine. Several derivatives of cocaine will be tested for cocaine-like effects to determine whether the N-methyl and/or the ester linkage of cocaine molecule are essential for the activities of cocaine.